SAT-009 - Desmopressin (DDAVP) Stimulation Test in Patients with Possible Cushing Syndrome

Background
Differentiating true tumoral hypercortisolemia (TTH) from non-neoplastic hypercortisolemia (NNH) is an unmet need. There are limited data on the accuracy of the DDAVP stimulation test (DDAVPST) for the diagnosis of TTH, particularly in cases with discrepant and/or cyclic findings. In addition, while the standard protocol is 120 minutes, the optimal duration is undetermined.

Purpose
The goals of this study were: 1) to evaluate the utility of the DDAVPST in distinguishing NNH from TTH in patients with ACTH-dependent hypercortisolemia and discrepant testing for Cushing Syndrome (CS) and 2) to determine the optimal duration for the DDAVPST.

Methods
NNH was confirmed by normalization of cortisol after reversal of depression, obesity, alcoholism, or other causes of NNH. Cushing Disease (CD) was confirmed by pathology and/or postsurgical remission. We analyzed the accuracy of the DDAVPST using predefined and optimal cut-points and calculated sensitivity, specificity, area under the curve (AUC), and performed receiver operating characteristic (ROC) analysis.

Results
A total of 94 patients with ACTH-dependent hypercortisolemia underwent a DDAVPST. A definitive diagnosis was established in 33 patients (29F/4M), 49.1±14.9 years (mean ±SD), BMI 36.2±10.8 kg/m2, followed for 12.8±10.8 months after DDAVPST. Sixty-one patients are still undergoing evaluation. CD and NNH were confirmed in 18 and 15 cases, respectively. In patients with CD, 15/18 (83.3%) had a positive test using predefined criteria of a baseline to peak ACTH delta ≥27 pg/ml, while 15/15 (100%) NNH cases had a negative test. The DDAVPST demonstrated a sensitivity and negative predictive value (NPV) of 83.3%, and a specificity and positive predictive value (PPV) of 100%. The optimal baseline to peak ACTH delta cut-point based on ROC was >25.5 pg/ml (AUC 0.937). The combined criteria of a peak ACTH≥37 pg/ml and/or a baseline to peak delta ACTH ≥27 pg/ml, achieved a higher sensitivity of 94.4%, an NPV of 93.8%, and a specificity and PPV of 100%. The mean delta ACTH from baseline to peak and the absolute peak ACTH were higher in CD than in NNH (51.4±30.8 vs. 9.4±8.8 pg/ml, p=0.007, and 94.8±3.8 vs. 21.7±9.4 pg/ml, p=0.002, respectively). Mean delta cortisol from baseline to peak and absolute peak cortisol were higher in CD than NNH (8.2±7.3 vs. 0.18±1.8 mcg/dL, p< 0.001, and 23.8±8.0 vs. 13.7±5.2 mcg/dL, p< 0.001). All CD patients achieved a peak ACTH by 45 minutes and a peak cortisol by 60 minutes.

Conclusions
In cases of hypercortisolemia and discrepant testing for CS, optimal DDAVPST cutoffs including the change from baseline to peak ACTH and absolute peak ACTH provide high diagnostic accuracy in distinguishing CD from NNH. This information is determined within the first hour of the DDAVPST, suggesting that longer testing duration is likely unnecessary.

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